The aim was to enhance the dissolution of lornoxicam (LOR) and to produce mini-tablets with an optimised system to provide a rapid-release multi-particulate formulation. LOR systems were prepared through co-evaporation with either polyethylene glycol 6000 or Pluronic® F-68 (PLU) and adsorption onto Neusilin® US2 alone or co-adsorption in the presence of different amounts of polysorbate 80. All systems were characterised by FT-IR, differential scanning calorimetry, X-ray diffraction, flowability and dissolution techniques. Mini-tablets were prepared using the system with the optimum dissolution profile and flowability. Tensile strengths, content uniformity and dissolution profiles of the mini-tablets were evaluated. The effects of different excipients and storage conditions on mini-tablet properties were also studied. The optimised rapid-release LOR mini-tablets were further evaluated for their in vivo pharmacokinetic profile. The co-evaporate of LOR with PLU showed significantly faster dissolution and superior flowability and was evaluated together with three directly compressible excipients (Cellactose® 80, StarLac® (STA) and Emcompress®) for mini-tablet formulation. The formulation with STA provided the optimum results in terms of tensile strength, content uniformity and rapid drug release following a 3-month stability study and was selected for further in vivo evaluation. The pharmacokinetic profile indicated the potential of the mini-tablets achieving rapid release and increased absorption of LOR.

An efficient synthesis of some new NSAIDs prodrugs viz., (S)-ethyl 2-[(S)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (1), (S)-ethyl 2-[(R)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (2), (S)-dimethyl 2-[2-(2,3-dimethylphenylamino)benzamido]-succinate (3) and (RS)-methyl-2-(2-(2,6-dichloro-3-methylphenylamino)benzamido)butanoate (4) with high purity were carried out by the amidation of RS-ibuprofen, mefenamic acid and meclofenamic acid with methyl ester and ethyl ester of amino acids L-leucine, L-aspartic acid and DL-2-aminobutyric acid. The products formed were confirmed by IR, 1H NMR, 13C NMR, HR MS (1-4) and single crystal X-ray crystallography analysis (2-4). Compound (2) crystallizes in orthorhombic space group P212121 with unit cell dimensions a = 5.1931 (2) Å, b = 10.0031 Å, c = 41.0764 (11) Å,  =  =  = 90°, V = 2133.80 (12) Å3, Z = 4. Compound (3) crystallizes in hexagonal space group P65 with unit cell dimensions a = 11.4965 (3) Å, b = 11.4965 (3) Å, c = 26.5323 (12) Å,  =  = 90°,  = 120°, V = 3036.94 (18) Å3, Z = 6. Compound (4) crystallizes in triclinic space group Pi with unit cell dimensions a = 8.7969 (3) Å, b = 10.6307 (3) Å, c = 11.8469 (4) Å,  = 76.724 (3)°,  = 89.066 (3)°,  = 66.169 (2)°, V = 982.70 (5) Å3, Z = 2.

A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with 3a showing IC50 of 11.4 µM (two orders of magnitude more potent than naproxen). Selectivity of 3a was investigated against a panel of three tumor and one normal colon cell lines and showed up to six times less toxicity against normal colonocytes. Compound 3a was shown to induce dose-dependent apoptosis of HT116 colon tumor cells as evidenced by measuring the activity of caspases-3 and 7. None of the synthesized compounds showed activity against COX-1 or COX-2 isozymes, confirming a COX-independent mechanism of action. Compound 3k was found to have no ulcerogenic effect in rats as indicated by electron microscope scanning of the stomach after oral administration. A pharmacophore model was developed for elucidating structure–activity relationships and subsequent chemical optimization for this series of compounds as colorectal cancer chemopreventive drugs.

A Snovel method for the simultaneous separation and determination of two antiglaucoma drugs namely, dorzolamide hydrochloride (DOR) and timolol maleate (TIM) in aqueous humor samples (AH) was developed by using salting-out assisted liquid–liquid microextraction (SALLME) combined with HPLC–UV method. Box–Behnken experimental design and response surface methodology were employed to assist the optimization of SALLME conditions, including salt concentration, the pH of sample solution and vortex time as variable factors. The optimal extraction conditions were as follows: to 50 µL of AH sample, 100 µL of phosphate buffer (100 mmolL-1, pH 11.9), 90 µL of acetonitrile (ACN) and 0.11 g of (NH4)2SO4 salt were added into an Eppendorf vial (1mL) then vortexed for 1.1 min. As an effort to miniaturize SALLE system, a 1 mL syringe adapted with a capillary tube was employed as the phase separation device. Once the phase separation occurred, the upper layer could be narrowed into the capillary tube by pushing the plunger; thus, the collection of the upper layer solvent was simple and convenient. By miniaturization, the consumption of the organic solvent was decreased as low as possible. The chromatographic separation was achieved on Gemini C18 column using a mobile phase of ACN: 30 mmolL-1 potassium dihydrogen phosphate buffer containing 0.1% triethylamine, pH 3.5 (20:80, v/v) at a flow rate of 1 mL min-1 and UV detection at 254 and 295 nm for DOR and TIM, respectively. Mepivacaine hydrochloride was used as an internal standard. The described method showed better separation with enhanced sensitivities than the previously reported methods with limits of quantitation of 8.75 and 10.32 ng mL-1 in aqueous solution and 15.97 and 23.53 ng mL-1 in AH for DOR and TIM, respectively. The simple, rapid and eco-friendly SALLME–HPLC method has been successfully applied for the simultaneous pharmacokinetic studies of DOR and TIM in rabbit AH.

A highly sensitive, selective and reproducible chromatographic method is described for determination of low-molecular mass unsaturated aliphatic aldehydes in human serum. The method combines fluorescent labeling using 4-(N,N-Dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole with peroxyoxalate chemiluminescence. The derivatives were separated on a reversed-phase column C8 isocratically using a mixture of acetonitrile and 90 mM imidazole–HNO3 buffer (pH 6.4, 1:1, % v/v). The calibration ranges were: 20–420 nM for methylglyoxal, 16–320 nM for acrolein, 15–360 nM for crotonaldehyde and 20–320 nM for trans-2-hexenal. The detection limits were ranged from 4.4 to 6.5 nM (88–130 fmol/injection), the recovery results were within the range of 87.4–103.8% and the intra and inter-day precision results were lower than 5.5%. The proposed validated method has been successfully applied to healthy, diabetic and rheumatic arthritis patients’ sera with simple pretreatment method. In conclusion, this new method is suitable for routine analysis of large numbers of clinical samples for assessment of the oxidative stress state in patients.

A highly sensitive, selective and reproducible chromatographic method is described for determination of low-molecular mass unsaturated aliphatic aldehydes in human serum. The method combines fluorescent labeling using 4-(N,N-Dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole with peroxyoxalate chemiluminescence. The derivatives were separated on a reversed-phase column C8 isocratically using a mixture of acetonitrile and 90 mM imidazole–HNO3 buffer (pH 6.4, 1:1, % v/v). The calibration ranges were: 20–420 nM for methylglyoxal, 16–320 nM for acrolein, 15–360 nM for crotonaldehyde and 20–320 nM for trans-2-hexenal. The detection limits were ranged from 4.4 to 6.5 nM (88–130 fmol/injection), the recovery results were within the range of 87.4–103.8% and the intra and inter-day precision results were lower than 5.5%. The proposed validated method has been successfully applied to healthy, diabetic and rheumatic arthritis patients’ sera with simple pretreatment method. In conclusion, this new method is suitable for routine analysis of large numbers of clinical samples for assessment of the oxidative stress state in patients.

A highly sensitive, selective and reproducible chromatographic method is described for determination of low-molecular mass unsaturated aliphatic aldehydes in human serum. The method combines fluorescent labeling using 4-(N,N-Dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole with peroxyoxalate chemiluminescence. The derivatives were separated on a reversed-phase column C8 isocratically using a mixture of acetonitrile and 90 mM imidazole–HNO3 buffer (pH 6.4, 1:1, % v/v). The calibration ranges were: 20–420 nM for methylglyoxal, 16–320 nM for acrolein, 15–360 nM for crotonaldehyde and 20–320 nM for trans-2-hexenal. The detection limits were ranged from 4.4 to 6.5 nM (88–130 fmol/injection), the recovery results were within the range of 87.4–103.8% and the intra and inter-day precision results were lower than 5.5%. The proposed validated method has been successfully applied to healthy, diabetic and rheumatic arthritis patients’ sera with simple pretreatment method. In conclusion, this new method is suitable for routine analysis of large numbers of clinical samples for assessment of the oxidative stress state in patients.

A highly sensitive, selective and reproducible chromatographic method is described for determination of low-molecular mass unsaturated aliphatic aldehydes in human serum. The method combines fluorescent labeling using 4-(N,N-Dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole with peroxyoxalate chemiluminescence. The derivatives were separated on a reversed-phase column C8 isocratically using a mixture of acetonitrile and 90 mM imidazole–HNO3 buffer (pH 6.4, 1:1, % v/v). The calibration ranges were: 20–420 nM for methylglyoxal, 16–320 nM for acrolein, 15–360 nM for crotonaldehyde and 20–320 nM for trans-2-hexenal. The detection limits were ranged from 4.4 to 6.5 nM (88–130 fmol/injection), the recovery results were within the range of 87.4–103.8% and the intra and inter-day precision results were lower than 5.5%. The proposed validated method has been successfully applied to healthy, diabetic and rheumatic arthritis patients’ sera with simple pretreatment method. In conclusion, this new method is suitable for routine analysis of large numbers of clinical samples for assessment of the oxidative stress state in patients.

4-Hydroxy-2-nonenal (4HNE) is a major aldehyde generated during lipid peroxidation. The clinical monitoring of 4HNE in biological fluids should be useful for the early diagnosis of several diseases involving lipid peroxidation, such as rheumatoid arthritis, Parkinson’s disease and cancer. In this study, an HPLC with fluorescence detection method was developed for the determination of 4HNE in human serum. The proposed method involves the extraction of 4HNE from human serum by sub-zero temperature extraction and fluorescent labeling of 4HNE with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2, 1,3-benzoxadiazole. The lower detection limit (signal-to-noise ratio = 3) of the method was 0.06 μM in serum. The proposed method was successfully applied to the measurement of 4HNE in sera obtained from patients with rheumatoid arthritis.

A radical scavenging guided phytochemical study on the leaf of Simmondsia chinensis afforded ten flavonoids (1–10) and four lignans (11–14). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Among isolated compounds, flavonoid aglycones (1–4) showed stronger antioxidant activity than their glycosides (5–10) whilst lignan glycosides (11–14) showed moderate to weak antioxidant activity using DPPH and -carotene methods in relation to BHT (positive control). The inhibitory potential against enzyme lipoxygenase was also evaluated for isolated compounds exhibiting variable potency. For flavonoids, glycosides are less potent inhibitors than free aglycones. Quercetin is the most potent inhibitor with an IC50 of 5.6 µM. Lignoid glycosides exhibited moderate to weak inhibitory effect against lipoxygenase enzyme. Luteolin was used as a positive control in lipoxygenase inhibiting assay.